Method of continuous capture verification in cardiac resynchronization devices

ABSTRACT

In bi-ventricular pacing devices (including CRT devices) analysis of myocardial electrogram signals in one ventricle (e.g., a left ventricle, or “LV”) can be used to infer capture or loss-of-capture (LOC) of an earlier stimulus pulse in the same ventricle, on a continuous (every pacing cycle), triggered, aperiodic and/or periodic basis. Rather than using an evoked-response principle as has been the basis of capture detection in prior art and other systems, a principle employed via the present invention uses evidence of inter-ventricular conduction (i.e., from the opposite chamber) and/or atrio-ventricular conduction as evidence of LOC, since a non-capturing pacing stimulus provided to a first chamber will allow the myocardial tissue of the first chamber to remain non-refractory and thus inter-ventricular and atrio-ventricular wavefront propagation and conduction can commence and be detected thereby revealing whether LOC has occurred.

PRIORITY CLAIM AND CROSS REFERENCE TO RELATED APPLICATIONS

This non-provisional U.S. patent application claims the benefit of thefiling of the following four (4) provisional U.S. patent applicationseach of which was filed on 20 Dec. 2004: a provisional application byKleckner et al.; namely Ser. No. 60/637,532 entitled, “LV THRESHOLDMEASUREMENT AND CAPTURE MANAGEMENT;” a provisional U.S. patentapplication by Mongeon et al.; namely Ser. No. 60/637,633 entitled“BI-VENTRICULAR VENTRICULAR CAPTURE MANAGEMENT IN CARDIACRESYNCRONIZATION THERAPY (CRT) DELIVERY DEVICES;” a provisional U.S.patent application by Sheldon et al.; namely Ser. No. 60/637,571entitled “METHOD OF CONTINUOUS CAPTURE VERIFICATIONS IN CARDIACRESYNCHRONIZATION DEVICES;” and a provisional U.S. patent application bySheth et al., namely Ser. No. 60/637,620 entitled “AUTOMATIC LV/RVCAPTURE VERIFICATION AND DIAGNOSTICS,” the contents of the forgoingapplications (including all appended exhibits) are hereby incorporatedby reference herein.

FIELD OF THE INVENTION

The invention pertains to cardiac pacing systems and relates toapparatus and methods for automatically verifying pacing capture of aventricular chamber. In particular, the invention relates toverification of pacing capture for both ventricular chambers during acardiac resynchronization therapy (CRT) delivery, such as abi-ventricular pacing therapy or unidirectional fusion-type CRTdelivery.

BACKGROUND OF THE INVENTION

Cardiac resynchronization cardiac pacing devices operate by eitherdelivering pacing stimulus to both ventricles or to one ventricle withthe desired result of a more or less simultaneous mechanical contractionand ejection of blood from the ventricles. However, due to a number offactors for a variety of patients such cardiac pacing systems may notalways effectively delivery CRT. For example, varying capturethresholds, pacing lead and/or electrode migration or dislodgement, timerequired for appropriate signal processing, confounding conductiondelays or conduction blockages, diverse electrode placement locations,and the like.

In either form of CRT delivery, whether fusion-based or the moretraditional bi-ventricular stimulation, confirming that pacing stimuluscaptures each paced ventricle is a very important clinical issue so thatthe desired benefits of the CRT are in fact delivered to a patient.

Assuming that the reader is familiar with bi-ventricular pacing, thefollowing should provide additional insight into the importance ofcapture detection in a fusion-based bi-ventricular pacing engine. Onepremise underlying fusion-based pacing is the notion that a fusion-basedevoked left ventricular (LV) depolarization enhances stroke volume inhearts where the right ventricle (RV) depolarizes first. This iscommonly due to intact atrio-ventricular (AV) conduction to the RV of apreceding intrinsic or evoked atrial depolarization wave front, andwherein the AV conducted depolarization of the LV is unduly delayed. Thefusion depolarization of the LV is attained by timing the delivery ofthe LV pace (LVp) pulse to follow the intrinsic depolarization of the RVbut to precede the intrinsic depolarization of the LV. Specifically, anRV pace (RVp) pulse is not delivered due to the inhibition of the RVpevent upon the sensing of RV depolarization (RVs), allowing naturalpropagation of the wave front and depolarization of the intraventricularseptum, while an LVp pulse is delivered in fusion with the RVdepolarization. For supporting mode switches to alternate pacingmodalities, fusion-based CRT delivery engines typically include at leastone electrode in each ventricle which allows such engines to be used inconjunction with the present invention, as will be apparent upon reviewof the following written description and drawings of the invention.

Left ventricular capture in particular is a clinical issue withpresent-generation (and foreseeable) CRT systems, due to acknowledgeddifficulty of maintaining stable lead situation in the cardiac venousanatomy. Since CRT delivery becomes ineffective (possibly evendeleterious) if LV capture is lost, diagnosis of dislodgment andmaintenance of capture are high priorities.

Cardiac Resynchronization Therapy (CRT) devices have been shown toimprove quality of life (QOL), exercise capacity and New York HeartAssociation (NYHA) heart failure class. The NYHA rating varies fromClass I to Class IV, as follows: Class I: patients with no limitation ofactivities; they suffer no symptoms from ordinary activities. Class II:patients with slight, mild limitation of activity; they are comfortablewith rest or with mild exertion. Class III: patients with markedlimitation of activity; they are comfortable only at rest. Class IV:patients who should be at complete rest, confined to bed or chair; anyphysical activity brings on discomfort and symptoms occur at rest.

Currently approved CRT devices incorporate bi-ventricular pacingtechnology with simultaneous pacing in the right ventricle (RV) and theleft ventricle (LV). Since the devices are implanted for the essentiallyonly to provide continuous bi-ventricular pacing therapy, it isimperative that the each pacing pulse stimulus delivered to the two LVand RV provide an evoked response (i.e., each stimulus delivered to aventricle “captures” the ventricle). Thus, if electrodes disposed inelectrical communication with a ventricle rapidly sense depolarizationwavefronts a control sequence for the pacing engine will inhibitventricular pacing. For example, such a situation occurs during rapidlyconducted atrial fibrillation (AF). When bi-ventricular pacing isinhibited the patient's symptoms of heart failure return, and cansometimes even worsen as compared to their pre-implant status.Similarly, if one of the pacing sites loses capture (e.g., the LV) thesubsequent RV-only pacing will prevent the patient from receiving theintended benefit of CRT delivery. To that end the inventors haveaddressed a need in the art regarding capture verification in heartfailure devices, such as bi-ventricular CRT devices that indicates whencapture is occurring in both the LV and the RV.

Presently, the only somewhat similar diagnostic available in CRT devicesis percent-ventricular pacing (% Vpacing), which indicates thepercentage of time bi-ventricular pacing therapy is being delivered;however, a limitation of the % Vpacing metric is that bi-ventricularpacing may be “occurring” close to 100% of the time but the LV chambermay not be captured at all. Currently, cardiac device specialists assessLV capture acutely during office visits by looking at the morphology ofan electrogram (EGM) or by temporarily setting pacing to RV-only andLV-only pacing. Current state of the art pacemakers (e.g., the Kappa®brand family of pacemakers provided by Medtronic, Inc.) incorporateventricular capture management algorithms. However, such algorithmsrequire specific circuitry and sensing capabilities to be able toperform this function that are not currently available in the CRTproducts. Also, the feasibility of this technology for LV capturemanagement has yet to be established. Note that the present invention isprimarily intended for ventricular capture verification, and is notdirected solely to ventricular capture management, although the benefitsof the invention advantageously contribute to both capture verificationand capture management, particularly of the left ventricle (LV).

A need therefore exists in the art to effectively chronically deliverventricular pacing therapies (including CRT) to patients who might nototherwise receive the full benefit of such therapies.

SUMMARY

In bi-ventricular pacing devices (including CRT devices) analysis ofmyocardial electrogram signals in one ventricle (e.g., a left ventricle,or herein “LV”) can be used to infer capture or loss-of-capture (LOC) ofan earlier stimulus pulse in the same ventricle, on a continuous (everypacing cycle) or periodic basis. Rather than using an evoked-responseprinciple as has been the basis of capture detection in prior art andother systems, a principle employed by the present invention usesevidence of inter-ventricular conduction (i.e., from the oppositechamber) as evidence of LOC, since a non-capturing pacing stimulusprovided to a first chamber will allow the myocardial tissue of thefirst chamber to remain non-refractory and thus inter-ventricular (oratrio-ventricular) wavefront propagation and conduction will commence.The time interval from delivery of the pacing stimulus to detection ofthe evoked or intrinsic, inter-ventricular response can be compared to anominal threshold or a threshold particularly chosen for a givenpatient. In addition, the time intervals can vary depending on recent orpresent heart rate, activity sensor output signal(s), pacing mode andthe like.

To perform LOC determination for both ventricles during a single cardiaccycle each ventricle receives a pacing stimulus at approximately, orprecisely, the same moment. Assuming no so-called blanking periodimposed upon any sense amplifiers operatively coupled to each chamber,each captured chamber would more or less instantaneously respond to thelocally delivered supra-threshold pacing stimuli. Thus, each chamberwould become refractory for a time interval (until repolarizationoccurs). However, if one or both pacing stimuli is sub-threshold (e.g.,too low amplitude and/or pulse width, etc.) a sensed ventricular eventoccurring in any non-captured chamber will likely occur subsequent (bymore than 25 or 50 ms) to the pacing therapy delivery.

Using existing sense amplifiers and associated circuitry, simple andefficient signal analysis, and discrimination of the conducted signal ofinterest (from unwanted signals of cardiac activity such as T-waves,premature ventricular contractions, or “PVCs,” far-field R-waves, andthe like) can be enhanced as needed based on the timing the sensedsignal, its magnitude or other morphology characteristics, as registeredby suitable circuitry.

Ventricular sensing of intrinsic (not evoked) depolarization signal isthus used to infer LOC, as a basis for diagnostic and auto-adjustment ofstimulus output, in CRT or multi-site bradycardia therapy device.

The foregoing and other aspects and features of the present inventionwill be more readily understood from the following detailed descriptionof the embodiments thereof, when considered in conjunction with thedrawings, in which like reference numerals indicate similar structuresthroughout the several views.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an illustration of transmission of a normal cardiac conductionsystem through which depolarization waves are propagated through theheart in a normal intrinsic electrical activation sequence.

FIG. 2 is a schematic diagram depicting a three channel, atrial andbi-ventricular, pacing system for implementing the present invention.

FIG. 3 is a simplified block diagram of one embodiment of IPG circuitryand associated leads employed in the system of FIG. 2 for providingthree sensing channels and corresponding pacing channels usable inconjunction with the present invention.

FIG. 4 illustrates an embodiment of the continuous ventricular captureverification according to the present invention.

DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS

In the following detailed description, references are made toillustrative embodiments for carrying out methods of confirming pacingcapture of ventricular pacing stimulation. It is understood that otherembodiments may be utilized without departing from the scope of theinvention. For example, the invention is disclosed in detail herein inthe context of a bi-ventricular CRT delivery. In one form of theinvention, a bi-ventricular pacing regimen susceptible of continuouscapture verification is based on the principle that delivery of pacingstimulus sufficient to capture each ventricle should precludeinter-ventricular conduction due to the fact that each ventricle isrefractory following the evoked depolarization

Thus, ventricular sensing in a first ventricle (or both ventricles)following pacing stimulus delivery to both ventricles can be used on abeat-to-beat basis or can be invoked as desired to verify pacing captureof said ventricles. Thus, loss-of-capture (LOC) can be declared,verified or managed and one of several possible responses initiated. Forexample, the pacing pulse stimulus can be adjusted (e.g., modified pulseamplitude, pulse width, polarity, frequency, etc.), a pacing mode-switchcan be implemented, and/or in relatively extreme cases a clinician canattempt to adjust the system, including electrode location, to improvepacing capture.

A cardiac pacing apparatus, according to the invention, comprises aprogrammable implantable pulse generator (IPG) that can be operated as adual- or triple-chamber pacing system having an AV synchronous operatingmode for restoring upper and lower heart chamber synchronization and/orright and left atrial and/or ventricular chamber depolarizationsynchrony. A system according to the invention efficiently providescardiac resynchronization therapy (CRT) with a single ventricularstimulus per cardiac cycle in a fusion-inducing CRT delivery or with apair of synchronized bi-ventricular pacing stimulus per cardiac cycle.

The present invention provides enhanced hemodynamic performance forpatients that benefit from CRT delivery due to various forms of heartfailure, ventricular dysfunctions and/or ventricular conductionabnormalities. Pacing systems according to the present invention canalso include rate responsive features and anti-tachyarrhythmia pacingand the like. In addition, a system according to the invention caninclude cardioversion and/or defibrillation therapy delivery.

In accordance with an aspect of the present invention, a method andapparatus is provided to mimic the normal depolarization-repolarizationcardiac cycle sequence (nominally depicted in FIG. 1) and restorecardiac intra- and/or inter-ventricular synchrony between the RV and LVthat contributes to adequate cardiac output related to the synchronizedelectromechanical performance of the RV and LV. The foregoing and otheradvantages of the invention are realized through confirmed delivery ofcardiac pacing stimulation to the ventricles. For example, a number ofphysiologic factors can influence the ability of delivered pacingstimulus to capture a cardiac chamber. For instance, conduction delaysthrough the A-V node and/or the His-Purkinje fibers, electricalconduction delay for sensing intra-cardiac events (from electrodesthrough threshold sensing circuitry of a medical device), electricalconduction delay for pacing therapy delivery circuitry,electro-mechanical delay associated with the delivery of a pace and theensuing mechanical contraction, ischemic episodes temporarily temperingconduction pathways, myocardial infarction(s) zones, all candeleteriously impact cardiac conduction and thereby affect an operatingpacing therapy delivery regime. Because the conduction status of apatient can vary over time and/or vary based on other factors such asheart rate, autonomic tone and metabolic status, the present inventionprovides a dynamically controllable resynchronization pacing modality.

According to the invention verification of capture can be triggered sothat a desired amount of dual- or single-chamber (fusion-based) CRTdelivery ensues. Some of the factors include, (i) completion of apre-set number of cardiac cycles, (ii) pre-set time limit, (iii) loss ofcapture of a paced ventricle, (iv) physiologic response triggers (e.g.,systemic or intra-cardiac pressure fluctuation, heart rate excursion,metabolic demand increase, decrease in heart wall acceleration,intra-cardiac electrogram morphology or timing, etc.) and/or (v) time ofday, and the like. The present invention provides a cardiac pacingsystem that can readily compensate for the particular implantation sitesof the pace/sense electrode pair operatively coupled to a ventricularchamber. When implemented in a triple-chamber embodiment, a pacingsystem according to the present invention can quickly mode-switch in theevent that loss-of-capture (LOC) is declared.

FIG. 2 is a schematic representation of an implanted, triple-chambercardiac pacemaker comprising a pacemaker IPG 14 and associated leads16,32,52 in which the present invention may be practiced. The pacemakerIPG 14 is implanted subcutaneously in a patient's body between the skinand the ribs. The three endocardial leads 16,32,52 operatively couplethe IPG 14 with the RA, the RV and the LV, respectively. Each lead hasat least one electrical conductor and pace/sense electrode, and a remoteindifferent can electrode 20 is formed as part of the outer surface ofthe housing of the IPG 14. As described further below, the pace/senseelectrodes and the remote indifferent can electrode 20 (IND_CANelectrode) can be selectively employed to provide a number of unipolarand bipolar pace/sense electrode combinations for pacing and sensingfunctions, particularly sensing far field signals (e.g. far fieldR-waves). The depicted positions in or about the right and left heartchambers are also merely exemplary. Moreover other leads and pace/senseelectrodes may be used instead of the depicted leads and pace/senseelectrodes that are adapted to be placed at electrode sites on or in orrelative to the RA, LA, RV and LV. Also, multiple electrodes and/orleads may be deployed into operative communication with a relatively“late” depolarizing ventricle to pace at one or multiple sites withvarying degrees of pre-excitation in an effort to produce fusion of anintrinsic depolarization as described in U.S. Pat. No. 6,871,096 to Hilland non-provisional U.S. application Ser. No. 10/803,570 to Mullen andBurnes, the contents of which are incorporated herein. In addition,mechanical and/or metabolic sensors can be deployed independent of, orin tandem with, one or more of the depicted leads. In the event thatmultiple pacing electrodes are operatively deployed into communicationwith a single chamber, a capture detection for each such electrode maybe individually performed. That is, different pacing stimulus can beimplemented for each discrete pacing location and said pacing stimulusdelivery can thus be tuned for capture and/or conduction anomalies(e.g., due to infarct or ischemia or the like).

As depicted, a bipolar endocardial RA lead 16 passes through a vein intothe RA chamber of the heart 10, and the distal end of the RA lead 16 isattached to the RA wall by an attachment mechanism 17. The bipolarendocardial RA lead 16 is formed with an in-line connector 13 fittinginto a bipolar bore of IPG connector block 12 that is coupled to a pairof electrically insulated conductors within lead body 15 and connectedwith distal tip RA pace/sense electrode 19 and proximal ring RApace/sense electrode 21. Delivery of atrial pace pulses and sensing ofatrial sense events is effected between the distal tip RA pace/senseelectrode 19 and proximal ring RA pace/sense electrode 21, wherein theproximal ring RA pace/sense electrode 21 functions as an indifferentelectrode (IND_RA). Alternatively, a unipolar endocardial RA lead couldbe substituted for the depicted bipolar endocardial RA lead 16 and beemployed with the IND_CAN electrode 20. Or, one of the distal tip RApace/sense electrode 19 and proximal ring RA pace/sense electrode 21 canbe employed with the IND_CAN electrode 20 for unipolar pacing and/orsensing.

Bipolar, endocardial RV lead 32 is passed through the vein and the RAchamber of the heart 10 and into the RV where its distal ring and tip RVpace/sense electrodes 38 and 40 are fixed in place in the apex by aconventional distal attachment mechanism 41. The RV lead 32 is formedwith an in-line connector 34 fitting into a bipolar bore of IPGconnector block 12 that is coupled to a pair of electrically insulatedconductors within lead body 36 and connected with distal tip RVpace/sense electrode 40 and proximal ring RV pace/sense electrode 38,wherein the proximal ring RV pace/sense electrode 38 functions as anindifferent electrode (IND_RV). Alternatively, a unipolar endocardial RVlead could be substituted for the depicted bipolar endocardial RV lead32 and be employed with the IND_CAN electrode 20. Or, one of the distaltip RV pace/sense electrode 40 and proximal ring RV pace/sense electrode38 can be employed with the IND_CAN electrode 20 for unipolar pacingand/or sensing.

Further referring to FIG. 2, a bipolar, endocardial coronary sinus (CS)lead 52 is passed through a vein and the RA chamber of the heart 10,into the coronary sinus and then inferiorly in a branching vessel of thegreat cardiac vein to extend the proximal and distal LV CS pace/senseelectrodes 48 and 50 alongside the LV chamber. The distal end of such aCS lead is advanced through the superior vena cava, the right atrium,the ostium of the coronary sinus, the coronary sinus, and into acoronary vein descending from the coronary sinus, such as the lateral orposteriolateral vein. In addition, while not depicted in FIG. 2 theatrial, ventricular, and/or CS-deployed pacing leads can couple to theexterior of a heart via a pericardial or epicardial attachmentmechanism.

In a four chamber or channel embodiment, LV CS lead 52 bears proximal LACS pace/sense electrodes 28 and 30 positioned along the CS lead body tolie in the larger diameter CS adjacent the LA. Typically, LV CS leadsand LA CS leads do not employ any fixation mechanism and instead rely onthe close confinement within these vessels to maintain the pace/senseelectrode or electrodes at a desired site. The LV CS lead 52 is formedwith a multiple conductor lead body 56 coupled at the proximal endconnector 54 fitting into a bore of IPG connector block 12. A smalldiameter lead body 56 is selected in order to lodge the distal LV CSpace/sense electrode 50 deeply in a vein branching from the great vein(GV).

In this case, the CS lead body 56 would encase four electricallyinsulated lead conductors extending proximally from the more proximal LACS pace/sense electrode(s) and terminating in a dual bipolar connector54. The LV CS lead body would be smaller between the LA CS pace/senseelectrodes 28 and 30 and the LV CS pace/sense electrodes 48 and 50. Itwill be understood that LV CS lead 52 could bear a single LA CSpace/sense electrode 28 and/or a single LV CS pace/sense electrode 50that are paired with the IND_CAN electrode 20 or the ring electrodes 21and 38, respectively for pacing and sensing in the LA and LV,respectively.

In this regard, FIG. 3 depicts bipolar RA lead 16, bipolar RV lead 32,and bipolar LV CS lead 52 without the LA CS pace/sense electrodes 28 and30 coupled with an IPG circuit 300 having programmable modes andparameters of a bi-ventricular DDD/R type known in the pacing art. Inturn the sensor signal processing circuit 43 indirectly couples to thetiming circuit 330 and via bus 306 to microcomputer circuitry 302. TheIPG circuit 300 is illustrated in a functional block diagram dividedgenerally into a microcomputer circuit 302 and a pacing circuit 320. Thepacing circuit 320 includes the digital controller/timer circuit 330,the output amplifiers circuit 340, the sense amplifiers circuit 360, theRF telemetry transceiver 322, the activity sensor circuit 322 as well asa number of other circuits and components described below.

Crystal oscillator circuit 338 provides the basic timing clock for thepacing circuit 320, while battery 318 provides power. Power-on-resetcircuit 336 responds to initial connection of the circuit to the batteryfor defining an initial operating condition and similarly, resets theoperative state of the device in response to detection of a low batterycondition. Reference mode circuit 326 generates stable voltage referenceand currents for the analog circuits within the pacing circuit 320,while analog to digital converter ADC and multiplexer circuit 328digitizes analog signals and voltage to provide real time telemetry if acardiac signals from sense amplifiers 360, for uplink transmission viaRF transmitter and receiver circuit 332. Voltage reference and biascircuit 326, ADC and multiplexer 328, power-on-reset circuit 336 andcrystal oscillator circuit 338 may correspond to any of those presentlyused in current marketed implantable cardiac pacemakers.

If the IPG is programmed to a rate responsive mode, the signals outputby one or more physiologic sensor are employed as a rate controlparameter (RCP) to derive a physiologic escape interval. For example,the escape interval is adjusted proportionally the patient's activitylevel developed in the patient activity sensor (PAS) circuit 322 in thedepicted, exemplary IPG circuit 300. The patient activity sensor 316 iscoupled to the IPG housing and may take the form of a piezoelectriccrystal transducer as is well known in the art and its output signal isprocessed and used as the RCP. Sensor 316 generates electrical signalsin response to sensed physical activity that are processed by activitycircuit 322 and provided to digital controller/timer circuit 330.Activity circuit 332 and associated sensor 316 may correspond to thecircuitry disclosed in U.S. Pat. Nos. 5,052,388 and 4,428,378.Similarly, the present invention may be practiced in conjunction withalternate types of sensors such as oxygenation sensors, pressuresensors, pH sensors and respiration sensors, all well known for use inproviding rate responsive pacing capabilities. Alternately, OT time maybe used as the rate indicating parameter, in which case no extra sensoris required. Similarly, the present invention may also be practiced innon-rate responsive pacemakers.

Data transmission to and from the external programmer is accomplished bymeans of the telemetry antenna 334 and an associated RF transceiver 332,which serves both to demodulate received downlink telemetry and totransmit uplink telemetry. Uplink telemetry capabilities will typicallyinclude the ability to transmit stored digital information, e.g.operating modes and parameters, EGM histograms, and other events, aswell as real time EGMs of atrial and/or ventricular electrical activityand Marker Channel pulses indicating the occurrence of sensed and paceddepolarizations in the atrium and ventricle, as are well known in thepacing art.

Microcomputer 302 contains a microprocessor 304 and associated systemclock 308 and on-processor RAM and ROM chips 310 and 312, respectively.In addition, microcomputer circuit 302 includes a separate RAM/ROM chip314 to provide additional memory capacity. Microprocessor 304 normallyoperates in a reduced power consumption mode and is interrupt driven.Microprocessor 304 is awakened in response to defined interrupt events,which may include A-TRIG, RV-TRIG, LV-TRIG signals generated by timersin digital timer/controller circuit 330 and A-EVENT, RV-EVENT, andLV-EVENT signals generated by sense amplifiers circuit 360, amongothers. The specific values of the intervals and delays timed out bydigital controller/timer circuit 330 are controlled by the microcomputercircuit 302 by means of data and control bus 306 from programmed-inparameter values and operating modes. In addition, if programmed tooperate as a rate responsive pacemaker, a timed interrupt, e.g., everycycle or every two seconds, may be provided in order to allow themicroprocessor to analyze the activity sensor data and update the basicA-A, V-A, or V-V escape interval, as applicable. In addition, themicroprocessor 304 may also serve to define variable, operative AV delayintervals and the energy delivered to each ventricle.

In one embodiment of the invention, microprocessor 304 is a custommicroprocessor adapted to fetch and execute instructions stored inRAM/ROM unit 314 in a conventional manner. It is contemplated, however,that other implementations may be suitable to practice the presentinvention. For example, an off-the-shelf, commercially availablemicroprocessor or microcontroller, or custom application-specific,hardwired logic, or state-machine type circuit may perform the functionsof microprocessor 304.

Digital controller/timer circuit 330 operates under the general controlof the microcomputer 302 to control timing and other functions withinthe pacing circuit 320 and includes a set of timing and associated logiccircuits of which certain ones pertinent to the present invention aredepicted. The depicted timing circuits include URI/LRI timers 364, V-Vdelay timer 366, intrinsic interval timers 368 for timing elapsedV-EVENT to V-EVENT intervals or V-EVENT to A-EVENT intervals or the V-Vconduction interval, escape interval timers 370 for timing A-A, V-A,and/or V-V pacing escape intervals, an AV delay interval timer 372 fortiming the A-LVp delay (or A-RVP delay) from a preceding A-EVENT orA-TRIG, a post-ventricular timer 374 for timing post-ventricular timeperiods, and a date/time clock 376.

According to the invention, the AV delay interval timer 372 is loadedwith an appropriate delay interval for one ventricular chamber (i.e.,either an A-RVp delay or an A-LVp delay to time-out starting from apreceding A-PACE or A-EVENT. The interval timer 372 triggers pacingstimulus delivery, and can based on one or more prior cardiac cycles (orfrom a data set empirically derived for a given patient)

The post-event timers 374 time out the post-ventricular time periodsfollowing an RV-EVENT or LV-EVENT or a RV-TRIG or LV-TRIG andpost-atrial time periods following an A-EVENT or A-TRIG. The durationsof the post-event time periods may also be selected as programmableparameters stored in the microcomputer 302. The post-ventricular timeperiods include the PVARP, a post-atrial ventricular blanking period(PAVBP), a ventricular blanking period (VBP), and a ventricularrefractory period (VRP). The post-atrial time periods include an atrialrefractory period (ARP) during which an A-EVENT is ignored for thepurpose of resetting any AV delay, and an atrial blanking period (ABP)during which atrial sensing is disabled. It should be noted that thestarting of the post-atrial time periods and the AV delays can becommenced substantially simultaneously with the start or end of eachA-EVENT or A-TRIG or, in the latter case, upon the end of the A-PACEwhich may follow the A-TRIG. Similarly, the starting of thepost-ventricular time periods and the V-A escape interval can becommenced substantially simultaneously with the start or end of theV-EVENT or V-TRIG or, in the latter case, upon the end of the V-PACEwhich may follow the V-TRIG. The microprocessor 304 also optionallycalculates AV delays, post-ventricular time periods, and post-atrialtime periods that vary with the sensor based escape interval establishedin response to the RCP(s) and/or with the intrinsic atrial rate.

The output amplifiers circuit 340 contains a RA pace pulse generator(and a LA pace pulse generator if LA pacing is provided), a RV pacepulse generator, and a LV pace pulse generator or corresponding to anyof those presently employed in commercially marketed cardiac pacemakersproviding atrial and ventricular pacing. In order to trigger generationof an RV-PACE or LV-PACE pulse, digital controller/timer circuit 330generates the RV-TRIG signal at the time-out of the A-RVP delay (in thecase of RV pre-excitation) or the LV-TRIG at the time-out of the A-LVpdelay (in the case of LV pre-excitation) provided by AV delay intervaltimer 372 (or the V-V delay timer 366). Similarly, digitalcontroller/timer circuit 330 generates an RA-TRIG signal that triggersoutput of an RA-PACE pulse (or an LA-TRIG signal that triggers output ofan LA-PACE pulse, if provided) at the end of the V-A escape intervaltimed by escape interval timers 370.

The output amplifiers circuit 340 includes switching circuits forcoupling selected pace electrode pairs from among the lead conductorsand the IND_CAN electrode 20 to the RA pace pulse generator (and LA pacepulse generator if provided), RV pace pulse generator and LV pace pulsegenerator. Pace/sense electrode pair selection and control circuit 350selects lead conductors and associated pace electrode pairs to becoupled with the atrial and ventricular output amplifiers within outputamplifiers circuit 340 for accomplishing RA, LA, RV and LV pacing.

The sense amplifiers circuit 360 contains sense amplifiers correspondingto any of those presently employed in contemporary cardiac pacemakersfor atrial and ventricular pacing and sensing. As noted in theabove-referenced, commonly assigned, '324 patent, it has been common inthe prior art to use very high impedance P-wave and R-wave senseamplifiers to amplify the voltage difference signal which is generatedacross the sense electrode pairs by the passage of cardiacdepolarization wavefronts. The high impedance sense amplifiers use highgain to amplify the low amplitude signals and rely on pass band filters,time domain filtering and amplitude threshold comparison to discriminatea P-wave or R-wave from background electrical noise. Digitalcontroller/timer circuit 330 controls sensitivity settings of the atrialand ventricular sense amplifiers 360.

The sense amplifiers are typically uncoupled from the sense electrodesduring the blanking periods before, during, and after delivery of a pacepulse to any of the pace electrodes of the pacing system to avoidsaturation of the sense amplifiers. The sense amplifiers circuit 360includes blanking circuits for uncoupling the selected pairs of the leadconductors and the IND_CAN electrode 20 from the inputs of the RA senseamplifier (and LA sense amplifier if provided), RV sense amplifier andLV sense amplifier during the ABP, PVABP and VBP. The sense amplifierscircuit 360 also includes switching circuits for coupling selected senseelectrode lead conductors and the IND_CAN electrode 20 to the RA senseamplifier (and LA sense amplifier if provided), RV sense amplifier andLV sense amplifier. Again, sense electrode selection and control circuit350 selects conductors and associated sense electrode pairs to becoupled with the atrial and ventricular sense amplifiers within theoutput amplifiers circuit 340 and sense amplifiers circuit 360 foraccomplishing RA, LA, RV and LV sensing along desired unipolar andbipolar sensing vectors.

Right atrial depolarizations or P-waves in the RA-SENSE signal that aresensed by the RA sense amplifier result in a RA-EVENT signal that iscommunicated to the digital controller/timer circuit 330. Similarly,left atrial depolarizations or P-waves in the LA-SENSE signal that aresensed by the LA sense amplifier, if provided, result in a LA-EVENTsignal that is communicated to the digital controller/timer circuit 330.Ventricular depolarizations or R-waves in the RV-SENSE signal are sensedby a ventricular sense amplifier result in an RV-EVENT signal that iscommunicated to the digital controller/timer circuit 330. Similarly,ventricular depolarizations or R-waves in the LV-SENSE signal are sensedby a ventricular sense amplifier result in an LV-EVENT signal that iscommunicated to the digital controller/timer circuit 330. The RV-EVENT,LV-EVENT, and RA-EVENT, LA-SENSE signals may be refractory ornon-refractory, and can inadvertently be triggered by electrical noisesignals or aberrantly conducted depolarization waves rather than trueR-waves or P-waves.

To simplify the description herein, it will be assumed that thefollowing references to an “A-EVENT” and “A-PACE” will denote rightatrial activity. In the event that the left atrium is monitored (orstimulated), the reader should appreciate that the LA is referred to.

An operating mode 400 of IPG circuit 300 according to the presentinvention are depicted in the flow chart and described as follows. Atdecision step 402 a nominal ventricular capture test initiation triggeris implemented. Although as depicted the decision relates to a time ofday (i.e., 3:00 a.m.) decision step 402 can include any of a widevariety of temporal or event-based triggers. If the criteria at step 402is not met then the process continues to step 404 and no action istaken. If the decision is affirmative at step 402 then decision step 406is implemented wherein any of a variety of criteria for not proceedingwith the conduction test 400 are analyzed. If the designated criteriaare met then the test 400 does not proceed (at step 408). Representativecriteria includes the presence of an arrhythmia, high heart rate, highactivity sensor signal input, and the like. If the designated criteriais met then the test 400 proceeds (at step 410) by programming arelatively long A-V delay interval so that the patient's PR interval(i.e., A-event to ventricular depolarization) emerges. The measured PRinterval is stored in a computer memory or the like.

Then at step 412 the pacing therapy mode-switches to (or implements) asingle ventricular pacing therapy with a relatively short (or minimum)A-V delay interval for at least one cardiac cycle. Then at step 414 ifno ventricular sense event (R-sense) occurs in the non-paced ventricleprior to a next-scheduled pacing stimulus delivery, then the method 400proceeds to step 416 wherein the result of step 414 is evaluated to seeif a similar event had occurred in the recent past (e.g., on a givenday, within a temporal window, more than once, etc.) which if positivethe method 400 returns to step 412. If the lack of an V-sense event isnot the first occurrence in a given day, for example, then the method400 proceed to step 424 wherein the pacing therapy delivery is labeledas loss-of-capture (LOC) before proceeding to step 434, ending themethod 400 until a later iteration occurs.

Following a positive result from decision step 414 the method 400proceeds to decision step 418 wherein the temporal location of theR-sense event is evaluated whether or not it occurred within a shorttime of the patient's PR interval (e.g., within about 40 ms less thanthe PR measured interval) is considered. In the event that the V-senseevent occurs within a physiologically short period of time before theexpiration of the patient's PR interval then at step 420 the V-sensedevent is queried whether it was the first such event in the recent past(e.g., on a given day, etc.) and if answered in the affirmative then themethod 400 returns to step 412—as described herein. If not, then thepacing regimen is declared as pacing “capture verified” (or equivalent)at step 432.

However, in the that the V-sense event occurs outside thephysiologically short period of time before the expiration of thepatient's PR interval then the method 400 proceeds to step 422 theV-sensed event is queried whether it was the first such event in therecent past (e.g., on a given day, etc.) and if answered in theaffirmative then the method 400 proceeds to step 426 where the R-senseevent is compared to a typical physiologic ventricular depolarizationfollowing an A-event (e.g., did the V-sense event register at a momentgreater than about 310 ms following the A-event. If step 426 is answeredin the affirmative then a pacing regimen LOC is declared at step 428 andthe method 400 ends at step 434. If step 426 is answered in the negativethen the pacing regimen is classified as likely not valid (e.g.,“capture suspect” or equivalent) and an optional message logged (at step430) that the patient's, or device, history merits review and then themethod 400 ends at step 434 until the method is later invoked to verifywhether ventricular pacing stimuli captures as intended.

The particular operating mode of the present invention is a programmedor hard-wired sub-set of possible CRT delivery operating modes,including bi-ventricular pacing whether involving simultaneous V-Vpacing stimulation (i.e., synchronized ventricular pacing therapydelivery) or offset V-V pacing stimulation (e.g., in an attempt tocompensate for various cardiac conduction and/or contractile defects).In addition, the invention can be used to verify pacing capture ofeither one of an RV or an LV (and RA and LA). As noted, the inventivealgorithm advantageously helps confirm the capture status of a pacingregimen by providing one of: a LOC signal, a capture signal, or a“capture suspect” signal. Of course, the methods according to thepresent invention are intended to be stored as executable instructionson any appropriate computer readable medium that provides controlsignals to effect the technical result of the invention herein describedand depicted, although certain of the steps of the inventive methods maybe performed manually as well.

Referring now to FIG. 4, one embodiment of the invention is depicted ina flow chart as method 400. Beginning at step 402 bi-ventricular pacingtherapy delivery to both ventricles occurs, with a nominal zero V-Voffset (i.e., not sequential CRT delivery). Then the ventricles aremonitored at step 404 to determine if the pacing therapy deliverycaptured one or both ventricles. At decision step 406 the ventricularsense events (Vs) are compared to determine if the Vs occurred within awindow of time too long to identify direct evoked activation but whichcan be positively identified as inter-ventricular conduction (e.g.,beginning at about 25 ms to about 55 ms). If the Vs event in eachventricle lies outside of this window then (at step 408) then the pacingstimulus is declared to be capturing the ventricle (at step 420).However, if at step 410 one ventricle (V1) produced a sensed event inthe “inter-ventricular conduction-sensing window” then at 414 the V1chamber is declared LOC. Then, optionally, at step 418 the pacing energydelivered can be increased and method 400 resumed at step 402. Likewise,if the V2 chamber detects activation during the inter-ventricularconduction-sensing window then the V2 chamber is declared to be LOC (andthe optional step 418 performed to return to step 402 at a differentenergy level).

While depicted in FIG. 4 as a single cycle bi-ventricular captureverification test one ventricle can be tested at a time according to theinvention. Also, the inter-ventricular conduction-sensing window canvary depending on a patient's physiology and present status (vis-à-visactivity, stress, drug regimen, etc.) and a given patient's LOC windowcan be identified acutely with any correlating parameters (e.g., in alook up table correlating heart rate, activity, etc. to theinter-ventricular conduction-sensing window).

In the presently described and depicted embodiment of the inventioncapture verification testing occurs on a beat-by-beat basis, however,the testing may occur based on a triggering signal (e.g., from a patientor clinician, from a hand-held programmer or the like locally orremotely spaced from said patient) or at a less frequent interval. Uponconfirmation of capture of a cardiac chamber, a desired pacing therapydelivery can be re-enabled and continue until: a loss of capture occurs,a predetermined period of time elapses, a mode-switch occurs to anotherpacing regimen (e.g., due to a automated physiologic trigger, aprogramming change, etc.) or the like. If a loss of capture in aventricular chamber is detected it could indicate one or more possibleproblems requiring remedial action. For example, the pacing electrodesmight have malfunctioned or become dislodged, an elongated conductorwithin a medical electrical lead might have been damaged, open- orshort-circuited. Accordingly, in addition to verifying pacing capture,the present invention optionally includes capability for alerting aphysician, clinician, patient, health care provider or the like thatpacing system interrogation might be required. In addition, theconfiguration of the pacing system, including collected patient data andphysiologic parameters can be stored for later retrieval therebyenhancing the likelihood of an accurate assessment of the operatingcondition of the pacing system.

In one form of the invention, following detection of inappropriate ornon-programmed operating conditions (e.g., including receipt of a LOCsignal during CRT delivery) the pacing therapy can be adjusted,discontinued or a mode switch performed to another pacing modalitywhich, for example might exclude the pacing lead that produced the LOCsignal. One aspect of this form of the invention, upon receipt of aventricular LOC signal an intended bi-ventricular or uni-ventricular CRTdelivery regimen is suspended and an atrial-pacing only therapy isimplemented (e.g., an AAI, ADI, AAI/R, ADI/R and the like). That is,assuming that a patient's A-V conduction remains relatively intact untilsuch time as the patient is able to receive qualified medical attentionor until a subsequent ventricular capture verification test indicatesthat non-suspect capture has been achieved. In this regard, U.S. Pat.No. 6,772,005 to Casavant et al. entitled “Preferred ADI/R: a PermanentPacing Mode to Eliminate Ventricular Pacing While Maintaining BackupSupport” which is assigned to Medtronic, Inc. is hereby incorporatedherein by reference in its entirety.

In a yet another related embodiment of the foregoing aspect of theinvention, in the event that a ventricular LOC signal persists amode-switch from a bi-ventricular CRT to a uni-ventricular, fusion-basedCRT can occur. In particular if the LOC signal relates to a heartfailure patient's first-to-depolarize ventricle such a uni-ventricular,fusion-based CRT delivery regimen characterized by pre-excitation of thesecond-to-depolarize ventricle can be chronically implemented. In thisregard pending non-provisional U.S. patent application Ser. No.10/803,570 filed 17 Mar. 2004 by J. Burnes and T. Mullen and entitled“APPARATUS AND METHODS OF ENERGY EFFICIENT, ATRIAL-BASED BI-VENTRICULARFUSION-PACING” is hereby incorporated herein by reference in itsentirety.

The patient may, in the best scenario, be relieved of pacing therapydelivery altogether (programming the pacing circuitry to an ODOmonitoring-only “pacing modality”). Assuming the patient is notchronotropically incompetent, normal sinus rhythm may emerge permanentlyfor all the activities of daily living. Additionally, the process 600may be employed to search for a change in conduction status (e.g.,wherein a later-to-depolarize ventricle changes from the LV to the RV).

It should be understood that, certain of the above-described structures,functions and operations of the pacing systems of the illustratedembodiments are not necessary to practice the present invention and areincluded in the description simply for completeness of an exemplaryembodiment or embodiments. It will also be understood that there may beother structures, functions and operations ancillary to the typicaloperation of an implantable pulse generator that are not disclosed andare not necessary to the practice of the present invention.

In addition, it will be understood that specifically describedstructures, functions and operations set forth in the above-referencedpatents can be practiced in conjunction with the present invention, butthey are not essential to its practice. It is therefore to beunderstood, that within the scope of the appended claims, the inventionmay be practiced otherwise than as specifically described withoutactually departing from the spirit and scope of the present invention.

1. A method of bi-ventricular pacing therapy, comprising: delivering atleast one pacing stimulus to a first ventricle via a least onepace/sense electrode disposed in electrical communication with saidfirst ventricle; delivering at least one pacing stimulus to a secondventricle via a least one pace/sense electrode disposed in electricalcommunication with said second ventricle; wherein the pacing stimuli aredelivered at approximately the same time; and in the event that adepolarization wavefront of the first ventricle is sensed in a firstinterval extending to between about 25 ms and about 55 ms after deliveryof the pacing stimulus to the first ventricle, declaring capture of saidfirst ventricle; in the event that a depolarization wavefront isdetected by the pace/sense electrode of the first ventricle within asecond interval following the first interval, following pacing delivery,then declaring loss-of-capture (LOC) of said first ventricle; and in theevent that a depolarization wavefront is detected by the pace/senseelectrodes of the second ventricle within a second interval followingthe first interval, following pacing delivery, then declaringloss-of-capture (LOC) of said second ventricle.
 2. A method according toclaim 1, further comprising: filtering signals related to senseddepolarization wavefronts.
 3. A method according to claim 2, wherein thefiltering of signals related to sensed depolarization wavefrontscomprises applying to the signals at least one of: a band-pass filteringstep, a high-pass filtering step, a low-pass filtering step, imposing atemporal blanking period.
 4. A method according to claim 1, wherein thebi-ventricular pacing therapy comprises a cardiac resynchronizationtherapy.
 5. A method according to claim 4, wherein the cardiacresynchronization therapy further comprises a fusion-based cardiacresynchronization therapy.
 6. A method according to claim 1, wherein themethod is performed periodically.
 7. A method according to claim 1,wherein the method is performed for a single cardiac cycle.
 8. A methodaccording to claim 1, wherein the method is performed substantiallycontinuously.
 9. A method according to claim 1, further comprising: uponreceiving the declaration of LOC, for at one subsequent cardiac cycle,repeating the claimed method.
 10. A method according to claim 1, furthercomprising: responsive to the declaration of LOC, for at least onesubsequent cardiac cycle, storing or measuring at least one of thefollowing operative pacing parameters: a pacing stimulus pulse width, apacing stimulus amplitude, a pacing stimulus polarity, a pacing stimulusfrequency.
 11. A method according to claim 1, further comprising:responsive to the declaration of LOC, for at least one subsequentcardiac cycle, storing or measuring at least one of the following pacingparameters: a pacing rate signal, a cardiac pressure output signal, aminute ventilation output signal, an activity sensor output signal, anacceleration output signal, a pulmonary edema parameter, a myocardialischemia parameter.
 12. A method according to claim 1, wherein the firstventricle consists of a left ventricular (LV) chamber and the pace/senseelectrode disposed in electrical communication with said first ventricleis disposed in a portion of one of: a coronary sinus, a portion of agreat vein, a portion of a vessel branching from the great vein.
 13. Amethod according to claim 12, wherein one of the at least one pacingpulses is delivered between: a tip and a ring pacing electrode, a pairof electrodes, a coil and a can-based electrode, a pair of coilelectrodes, an epicardial electrode and a second electrode, or asubcutaneous electrode and the second electrode.